AGE-DEPENDENT CHANGES OF GHRELIN-SENSITIVE NEURONS IN THE DORSOMEDIAL AND VENTROMEDIAL NUCLEI OF THE HYPOTHALAMUS IN RATS

The hypothalamus plays a central role in integrating the autonomic and somatic nervous systems with the endocrine system. The hormone ghrelin, acting via GHSR-1A receptor may play an important role in the regulation of aging. The expression of GHSR-1A was studied in the dorsomedial (DMN) and ventromedial (VMN) hypothalamic nuclei of young (2 months), mature (12 months), and aged (24 months) male Wistar rats using immunohistochemistry and extracellular in vivo electrophysiology. A small number of GHSR-1A-immunoreactive (IR) neurons were observed in the DMN (4.0±1.5%) and VMN (2.3±1.3%) in young rats, whereas the percentage of GHSR-1A-IR neurons significantly increased in mature (DMN - 22.1±2.8%, VMN – 25.5±4.4%) and aged rats (DMN - 24.8±2.8%, VMN – 26.5±3.8%). In all age groups, the median firing rate of DMN and VMN neurons did not change after ghrelin administration. In the DMN of young rats, ghrelin predominantly activated neurons (72%), whereas only a few neurons were inhibited by ghrelin (7%). In contrast, a large number of DMN neurons were inhibited by ghrelin in mature (50%) and aged rats (64%). In the VMN of young rats, the largest number of neurons were inhibited by ghrelin (52%), while the proportion of ghrelin-activated neurons increased, and the percentage of ghrelin-inhibited neurons decreased with aging in mature (40%) and aged rats (33%). These alterations may contribute to the development of age-related diseases, particularly metabolic syndrome.